Continuous metabolic syndrome score (siMS) enables quantification of severity of cardiometabolic affliction in individuals not presenting with metabolic syndrome.
Assessment of degree of cardiometabolic affliction in subjects not presenting with metabolic syndrome (MS) yet, would be helpful in the management of preventive health maintenance. To evaluate continuous metabolic syndrome score (siMS) in estimation of severity of cardiometabolic affliction in individuals not presenting with MS. We analyzed data from 3166 volunteers (56 % females) aged ≥ 16 years. siMS score was calculated as waist/height/0.5 + fasting plasma glucose (FPG)/5.6 + triacylglycerols (TAG)/1.7 + systolic blood pressure (SBP)/130 - high-density lipoprotein cholesterol (HDL-C)/1.02 (males) or 1.28 (females). In siMS quintiles, numbers of individuals presenting with 0-to-5 MS components were calculated. MS was considered as the presence of any 3 out of its 5 components. 33 % of participants without MS scored ≥ 4th quintile; 13 % of those free from MS components; 49 % of participants presenting with 1, and 83 % of those displaying 2 MS components. 11 % of individuals presented with MS, all but 1 displayed siMS within the 2 upper quintiles. Considerable proportion of individuals without MS presented with siMS in range displayed by individuals presenting with MS. SiMS might be useful in estimation of severity of cardiometabolic affliction prior to manifestation of MS, to identify individuals requiring early intervention to counteract developing pathological processes (Tab. 1, Ref. 21).


Spectral Response of Plasmonic Gold Nanoparticles to Capacitive Charging: Morphology Effects.
We report a study of the shape-dependent spectral response of the gold nanoparticle surface plasmon resonance at various electron densities to provide mechanistic insight into the role of capacitive charging, a topic of some debate. We demonstrate a morphology-dependent spectral response for gold nanoparticles due to capacitive charging using single-particle spectroscopy in an inert electrochemical environment. A decrease in plasmon energy and increase in spectral width for gold nanospheres and nanorods was observed as the electron density was tuned through a potential window of -0.3 to 0.1 V. The combined observations could not be explained by existing theories. A new quantum theory for charging based on the random phase approximation was developed. Additionally, the redox reaction of gold oxide formation was probed using single-particle plasmon voltammetry to reproduce the reduction peak from the bulk cyclic voltammetry. These results deepen our understanding of the relationship between optical and electronic properties in plasmonic nanoparticles and provide insight toward their potential applications in directed electrocatalysis.


PEP carboxykinase exchange reaction in photosynthetic bacteria.
This paper describes some new characteristics of the phosphoenolpyruvate carboxykinase CO(2)-oxaloacetate exchange reaction in purified preparations of Rhodospirillum rubrum. The enzymatic activity has been purified 169-fold. Nucleotide diphosphates substitute for nucleotide triphosphates in the exchange reaction. Nucleotide diphosphates will not support the synthesis of phosphoenolpyruvate from oxaloacetate. This reaction differs significantly from the CO(2)-oxaloacetate exchange reaction in higher plants and animals.


Mitochondrial dysfunction and oxidative stress in insulin resistance.
Evidence is mounting of the involvement of mitochondrial dysfunction in insulin resistance, diabetes and associated complications. This review aims to provide an overview of the effects of insulin resistance on mitochondrial function in several tissues. We consider the pathogenesis of insulin resistance from a mitochondrial perspective and contemplate potential beneficial effects of strategies aimed at modulating mitochondrial function in insulin resistance, including insulin and insulin-sensitizing drugs, antioxidants, and selectively targeting antioxidants to mitochondria.


What Influences Patient-Therapist Interactions in Musculoskeletal Physical Therapy? Qualitative Systematic Review and Meta-Synthesis.
Musculoskeletal physical therapy involves both specific and nonspecific effects. Nonspecific variables associated with the patient, therapist, and setting may influence clinical outcomes. Recent quantitative research has shown that nonspecific factors, including patient-therapist interactions, can influence treatment outcomes. It remains unclear, however, what factors influence patient-therapist interaction. This qualitative systematic review and meta-synthesis investigated patients' and physical therapists' perceptions of factors that influence patient-therapist interactions. Eleven databases were searched independently. Qualitative studies examining physical therapists' and patients' perceptions of factors that influence patient-therapist interactions in musculoskeletal settings were included. Two reviewers independently selected articles, assessed methodological quality using the Critical Appraisal Skills Programme (CASP), and performed the 3 stages of analysis: extraction of findings, grouping of findings (codes), and abstraction of findings. Thirteen studies were included. Four themes were perceived to influence patient-therapist interactions: (1) physical therapist interpersonal and communication skills (ie, presence of skills such as listening, encouragement, confidence, being empathetic and friendly, and nonverbal communication), (2) physical therapist practical skills (ie, physical therapist expertise and level of training, although the ability to provide good education was considered as important only by patients), (3) individualized patient-centered care (ie, individualizing the treatment to the patient and taking patient's opinions into account), and (4) organizational and environmental factors (ie, time and flexibility with care and appointments). Only studies published in English were included. A mix of interpersonal, clinical, and organizational factors are perceived to influence patient-therapist interactions, although research is needed to identify which of these factors actually influence patient-therapist interactions. Physical therapists' awareness of these factors could enhance patient interactions and treatment outcomes. Mechanisms to best enhance these factors in clinical practice warrant further study.


Wrinkling of Tympanic Membrane Under Unbalanced Pressure.
Mechanics of tympanic membrane (TM) is crucial for investigating the acoustic transmission through the ear. In this study, we studied the wrinkling behavior of tympanic membrane when it is exposed to mismatched air pressure between the ambient and the middle ear. The Rayleigh-Ritz method is adopted to analyze the critical wrinkling pressure and the fundamental eigenmode. An approximate analytical solution is obtained and validated by finite element analysis (FEA). The model will be useful in future investigations on how the wrinkling deformation of the TM alters the acoustic transmission function of the ear.


The long-term effect of pelvic osteotomy on birth canal size.
The effect of pelvic osteotomy on birth canal size at skeletal maturity is unknown. This information would be useful to counsel women of reproductive age who have undergone pelvic osteotomy. It was the purpose of this study to answer that question. A retrospective review of girls who had undergone pelvic osteotomy in the period 1980-1999 was performed. Transverse plane birth canal dimensions (inlet, mid-pelvis, and outlet) were measured from radiographs before and after osteotomy and at final follow-up. Final follow-up diameters were compared to threshold values (obstetric pelvimetry and clinical guidelines). There were 37 patients (40 osteotomies: 31 Salter, 5 Steel, 2 Chiari, and 2 Ganz). The average age at osteotomy was 7.5 +/- 5.3 years (range 2.0-21.3 years), and at final follow-up was 16.0 +/- 4.7 years (range 2.9-25.7 years); the average follow-up was 8.5 +/- 5.2 years (range 0.5-17.6 years). The effect of osteotomy at skeletal maturity was investigated by analyzing the 30 children > or = 14 years of age at the final follow-up. The pelvic inlet was above the threshold for all 30 children. The mid-pelvis was below the low normal threshold (9.5 cm) in 3 of 21 Salter, 2 of 5 Steel, and 1 of 2 Chiari osteotomies. The pelvic outlet was below the threshold in 2 of 21 Salter and 2 of 5 Steel osteotomies. The mid-pelvis dimensions were narrower in those who underwent osteotomy when older: 7.1 +/- 4.9 years (n = 24) and 11.9 +/- 7.9 years (n = 6) (p = 0.06) for those above and below the 9.5 cm mid-pelvis threshold, respectively. In conclusion, 6 of the 30 cases had a mid-pelvis which was below threshold at skeletal maturity. If the transverse mid-pelvis diameter at skeletal maturity is < 9.5 cm, then the likelihood of Cesarean section is increased, and this information should be given to the patient.


Supernumerary and supplemental teeth: case report.
This is to report the case of a ten year old child affected by a numeric dental anomaly showing the pathologic condition characterised by the simultaneous presence of supernumerary and supplemental teeth. The anomaly was analysed to plan the best surgical and orthodontic treatments. Dental history, clinical and instrumental examinations were made to perform a correct orthodontic examination and diagnosis. A young patient was affected by numeric dental anomaly in the upper jaw. We observed a high number of teeth, specifically two normally formed supplemental lateral permanent incisors and an unerupted mesiodens placed between the upper central incisors. Firstly, the supplemental lateral teeth were extracted. This surgical therapy and the application of a space maintainer were made to permit the eruption of the permanent canines. Then the mesiodens also underwent surgical treatment (i.e. extraction). Eventually, physiologic eruption of permanent teeth was allowed by the planned surgical-orthodontic treatment. Aim of the surgical-orthodontic treatment was extraction of the unerupted supernumerary teeth to obtain the physiologic eruption of the permanent ones. Orthodontic treatment is important to solve malocclusions and maintaining the space for the eruption of permanent teeth. Aesthetics and function are two important parameters in modern dentistry. All clinicians should try to make a correct and rational diagnosis for both simple and complex dental pathologies. Particularly in young children, invasive and surgical disinclusive techniques can be substituted by interceptive orthodontic treatments.


The pathway of subarachnoid CSF moving into the spinal parenchyma and the role of astrocytic aquaporin-4 in this process.
It has been proved that cerebrospinal fluid (CSF) in the subarachnoid space could reenter the brain parenchyma via the perivascular space. The present study was designed to explore the pathway of subarachnoid CSF flux into the spinal cord and the potential role of aquaporin-4 (AQP4) in this process. Fluorescently tagged cadaverine, for the first time, was used to study CSF movement in mice. Following intracisternal infusion of CSF tracers, the cervical spinal cord was sliced and prepared for fluorescence imaging. Some sections were subject with immunostaining in order to observe tracer distribution and AQP4 expression. Fluorescently tagged cadaverine rapidly entered the spinal cord. Tracer influx into the spinal parenchyma was time dependent. At 10min post-infusion, cadaverine was largely distributed in the superficial tissue adjacent to the pial surface. At 70min post-infusion, cadaverine was distributed in the whole cord and especially concentrated in the gray matter. Furthermore, fluorescent tracer could enter the spinal parenchyma either along the perivascular space or across the pial surface. AQP4 was observed highly expressed in the astrocytic endfeet surrounding blood vessels and the pial surface. Blocking AQP4 by its specific inhibitor TGN-020 strikingly reduced the inflow of CSF tracers into the spinal cord. Subarachnoid CSF could flow into the spinal cord along the perivascular space or across the pial surface, in which AQP4 is involved. Our observation provides a basis for the study on CSF movement in the spinal cord when some neurological diseases occur.


Topological Measurements of DWI Tractography for Alzheimer's Disease Detection.
Neurodegenerative diseases affect brain morphology and connectivity, making complex networks a suitable tool to investigate and model their effects. Because of its stereotyped pattern Alzheimer's disease (AD) is a natural benchmark for the study of novel methodologies. Several studies have investigated the network centrality and segregation changes induced by AD, especially with a single subject approach. In this work, a holistic perspective based on the application of multiplex network concepts is introduced. We define and assess a diagnostic score to characterize the brain topology and measure the disease effects on a mixed cohort of 52 normal controls (NC) and 47 AD patients, from Alzheimer's Disease Neuroimaging Initiative (ADNI). The proposed topological score allows an accurate NC-AD classification: the average area under the curve (AUC) is 95% and the 95% confidence interval is 92%-99%. Besides, the combination of topological information and structural measures, such as the hippocampal volumes, was also investigated. Topology is able to capture the disease signature of AD and, as the methodology is general, it can find interesting applications to enhance our insight into disease with more heterogeneous patterns.


Four-site skinfold anthropometry (FSA) versus body impedance analysis (BIA) in assessing nutritional status of patients on maintenance hemodialysis: which method is to be preferred in routine patient care?
Both four-site skinfold anthropometry (FSA) and bioelectrical impedance analysis (BIA) claim to be useful in routine clinical practice of maintenance dialysis as easy methods to assess nutritional status. The purpose of this study was to investigate which of these two methods is to be preferred. Both before and after dialysis nutritional and hydration status were evaluated by BIA in 20 stable hemodialysis patients. Variables of nutritional status as lean body mass (LBM) and body fat (BF) were assessed by four-site skinfold anthropometry (LBM-FSA and BF-FSA) and BIA (LBM-BIA and BF-BIA). Variables of hydration status were total body water (TBW), its distribution into intracellular and extracellular compartments (ICW and ECW, respectively) and ICW/ECW. Weight loss during dialysis correlated with a change of LBM-FSA (r = 0.75, p <0.005) and also with that of LBM-BIA (r = 0.69, p < 0.005). To promote reliability of follow-up measurements in intervention studies it is warranted to evaluate nutritional status in an unchanged hydration status. The highly significant correlation (r = 0.93, p < 0.005) between the two techniques and the comparability between means and SD indicate that both techniques were almost equivalent to each other, although, compared to LBM-BIA, LBM-FSA was less affected by changes in fluid status. The sam held true for BF-BIA and BF-FSA. BF-FSA correlated significantly with BF-BIA (r = 0.65, p <0.005), whereas no difference of mean +/- SD was found between BF-FSA and BF-BIA. FSA and BIA are almost comparable techniques to assess both LBM and BF, although FSA is less affected by changes in fluid status. However, assessing LBM in normohydration is mandatory. Compared with FSA, BIA is able to establish hydration status and lacks depency on operator interpretation. Therefore, in routine patient care the BIA technique is the one to be preferred.


A vignette-based evaluation of ChatGPT's ability to provide appropriate and equitable medical advice across care contexts.
ChatGPT is a large language model trained on text corpora and reinforced with human supervision. Because ChatGPT can provide human-like responses to complex questions, it could become an easily accessible source of medical advice for patients. However, its ability to answer medical questions appropriately and equitably remains unknown. We presented ChatGPT with 96 advice-seeking vignettes that varied across clinical contexts, medical histories, and social characteristics. We analyzed responses for clinical appropriateness by concordance with guidelines, recommendation type, and consideration of social factors. Ninety-three (97%) responses were appropriate and did not explicitly violate clinical guidelines. Recommendations in response to advice-seeking questions were completely absent (N = 34, 35%), general (N = 18, 18%), or specific (N = 44, 46%). 53 (55%) explicitly considered social factors like race or insurance status, which in some cases changed clinical recommendations. ChatGPT consistently provided background information in response to medical questions but did not reliably offer appropriate and personalized medical advice.


Justifying Conscience Clauses.
In "Disentangling Conscience Protections," in this issue of the Hastings Center Report, Nadia Sawicki offers a taxonomy of conscience protection laws (conscience clauses) that highlights the expansive protections they can offer to health professionals who refuse to provide a medical service for reasons of conscience. Conscience clauses can protect health professionals from adverse actions by public actors (such as administrative agencies, prosecutors, and government funders) or private actors (such as employers, private professional associations, and injured patients), and they can also protect health professionals from being subject to adverse actions for their beliefs, their conduct, or harm that results from their conduct. This taxonomy provides an accurate description of the broad range of protections conscience clauses can offer and thereby is a valuable contribution to the scholarly literature on conscientious objection in health care. But it remains to consider whether the distinctions Sawicki identifies disentangle conscience protections beyond merely providing a taxonomy. In particular, does the taxonomy identify relevant distinctions in relation to determining whether a conscience clause is justified?


Measles encephalopathy during immunosuppression: failure of interferon treatment.
Measles encephalopathy during immunosuppression (MEI) occurs in patients with immunologic defects and is fatal. The course of the disease in 2 children, 4 and 5 years old, in the remission phase of acute lymphatic leukemia is presented. Diagnosis was possible, post-mortem, by recognition of measles virus antigen in brain tissue and in one patient by demonstration of intrathecal production of measles antibodies. Treatment with interferon did not improve the condition. Preventive measures primarily by early immunization of the childhood population against measles is stressed.


Association of insulin-like growth factor binding protein-3 expression with melanoma progression.
Previous studies from our laboratory have identified several endothelial cell-associated marker genes implicated in human melanoma metastasis via tumor vasculogenic mimicry. In this study, we used dual model systems composed of melanoma cell lines and clinical melanoma samples to validate the importance of insulin-like growth factor binding protein-3 (IGFBP-3) as a marker involved in disease progression. Gene expression analysis was done using a microarray approach for both primary and metastatic melanoma samples. The expression of IGFBP-3 was decreased using a small interfering RNA (siRNA) knockdown approach and quantified with real-time quantitative reverse transcription-PCR analysis. The expression of insulin-like growth factor binding protein 3 (IGFBP-3) was up-regulated by nearly 16-fold in WM266-4 compared with WM35 cells. A subsequent parallel analysis using freshly isolated primary and metastatic melanoma cell samples and melanoma tissue array confirmed the previous findings. The functional significance of IGFBP-3 in melanoma invasion was further investigated using a siRNA gene knockdown approach, with the expression of IGFBP-3 markedly reduced. Additionally, siRNA knockdown resulted in a significant reduction in cell motility, migration, and invasive capacity of WM266-4 cells in vitro. These results strongly suggest that IGFBP-3 expression may be a vital cell motility, migration, and proliferation factor necessary for melanoma metastasis and is an important biomarker in human melanoma.


Efficacy and safety of naloxone in the management of postseizure complaints of tramadol intoxicated patients: a self-controlled study.
Tramadol has become a major cause of drug-induced seizure recently. Naloxone is reported to attenuate the seizurogenic activity of tramadol. Thus, the authors aimed to study the efficacy and safety of naloxone in the management of postseizure complaints. This self-controlled study was conducted from August 2006 to August 2008. 59 tramadol intoxicated patients who did have postseizure complaints entered the study. After initial resuscitation and work-up, they received intravenous naloxone 0.05 mg every 3-5 min, and the presence of symptoms, presence of abnormal waves in cerebral state monitor (CSM), cerebral state index (CSI) and optical density (OD) were assessed. 47 participants completed the study, of whom 43 (91%) had symptom resolution after the intervention, and the presence of symptoms was significantly different before and after the intervention (p<0.001). 47 patients had abnormal waves in the CSM before the intervention, while 15 had abnormal waves in the CSM after intervention (p<0.001). The baseline mean of CSI was 81 (SD: 5.17), which was significantly increased to 92 (SD: 2.35) after naloxone injection (p<0.001). The baseline mean of OD was 7.1 (SD: 0.23), which was significantly increased to 7.7 (SD: 0.29) after naloxone injection (p<0.001). Naloxone can be considered in the management of postseizure complaints of tramadol toxicity, but further rigorous studies are needed to provide sufficient evidence to support its routine use.


Evidence-Based Research in Complementary and Alternative Medicine III: Treatment of Patients with Alzheimer's Disease.
This paper presents the novel domain of evidence-based research (EBR) in the treatment of patients with Alzheimer's disease (AD) from the perspective of traditional medicine and of complementary and alternative medicine. In earlier lectures we have described the process of evidence-based medicine as a methodological approach to clinical practice that is directed to aid clinical decision-making. Here, we present a practical example of this approach with respect to traditional pharmacological interventions and to complementary and alternative treatments for patients with AD.


An Nphp1 knockout mouse model targeting exon 2-20 demonstrates characteristic phenotypes of human nephronophthisis.
Nephronophthisis (NPH) is the most prevalent monogenetic disorder leading to end-stage renal failure (ESRD) in childhood. Mutations in Nphp1, encoding a cilia-localized protein, account for the majority of NPH cases. Despite its identification many years ago, Nphp1 deletions targeting exon 4 or exon 20 have not reproduced the histological features of human NPH in murine models. In this study, we deleted exon 2-20 of Nphp1 by CRISPR/Cas9 gene editing to create a near-total knockout (KO) mouse model (Nphp1del2-20/del2-20). Nphp1del2-20/del2-20 mice faithfully reproduced the renal and extrarenal phenotypes associated with human NPH, including renal cyst development, tubular basement membrane thickening, retinal degeneration and abnormal spermatogenesis. Importantly, Nphp1 re-expression using an adenoviral-associated-virus-9 vector could partially rescue both renal and retinal phenotypes in Nphp1del2-20/del2-20 mice. Our results reported the first relevant Nphp1 mouse model with renal phenotypes for human disease. It will be a valuable model for future studies of Nphp1 function and to develop novel treatments for this common childhood disease.


Polypharmacy and adverse drug events among propensity score matched privately insured persons with and without spinal cord injury.
Retrospective quasi-experimental design. To compare the incidence of adverse drug events (ADEs) between persons with and without spinal cord injury (SCI), while controlling for all potential and available risk factors. A commercially available claims dataset consisting of ~170 million patient cases in the United States between 2012 and 2013. Participants (aged 18-64 years) included 2779 persons with polypharmacy and traumatic or non-traumatic SCI and 2779 propensity score-matched persons with polypharmacy without SCI. The cohorts were matched using demographic variables including number of concomitant prescriptions, comorbidities, hospital admissions, age, gender, and geographic region. Inpatient and outpatient claims records containing 395 distinct IDC-9 codes indicative of ADEs were extracted. Incidence and frequency of ADEs were compared between groups using logistic and Poisson regression, respectively. Persons with SCI were significantly more likely to experience an ADE than matched controls (Odds Ratio = 1.45, p < 0.0001). Among persons with ADEs (n = 1552), individuals with SCI experienced fewer ADEs over time than matched controls (Incidence Rate Ratio = 0.91, p < 0.0001). While persons with SCI and polypharmacy are at a greater risk for experiencing an ADE, their medical care after an ADE may be better managed than that of a matched control population. There may be a need for practice guidelines that facilitate proactive identification of persons with SCI at the highest risk of ADE. Steps may then be taken to mitigate risk, in contrast to current practice trends that appear to take a reactive approach after an ADE has occurred.


Uterine necrosis after laparoscopic uterine vessel dissection for symptomatic fibroid--a case report.
Laparoscopic dissection of uterine vessels is a new minimally invasive method to treat symptomatic fibroids. A potential complication of uterine artery dissection is uterine necrosis. A woman with a large intramural fibroid underwent laparoscopic dissection of the uterine vessels using ultrasonic activated shears and three months later developed focal uterine necrosis requiring exploratory laparotomy and supracervical hysterectomy. Although uterine artery coagulation and dissection are procedures with a low reported rate of complications, uterine fibroid or focal uterine necrosis can occur.


[Feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug Ⅲ].
Objective: To investigate the feasibility and efficacy of transcatheter closure of anastomotic leakage after aortic surgery using Amplatzer Vascular Plug Ⅲ (AVP Ⅲ). Methods: A retrospective analysis was performed in 5 patients with anastomotic leakage after aortic surgery, who underwent transcatheter closure in our hospital from January to June 2017 using AVP Ⅲ. Surgeries were performed in 3 cases of Standford type A dissection, 1 case of ascending aortic aneurysm and 1 case of persistent truncus.There were 3 males,and age was (43.8±13.1) years old. Anastomotic leakages located at the ascending aorta in 4 patients, and the other one located between the aortic arch and the stent-graft.Three of them had aorta-right atrium fistula and patients suffered from progressive heart failure. False aneurysm between aorta and pulmonary artery was formed in 1 patient, and patent aortic false lumenwas found in the other patient. All the AVP Ⅲ were deployed based on a femoral arteriosus loop. Patients were followed up after transcatheter closure to observe the clinical results. Results: Six AVP Ⅲ were successfully implanted in the 5 patients. Trivial residual shunt was seen in 1 patient after closure. The patients were followed up 6 (1, 6) months. The cardiac function improved from NYHA class Ⅱ-Ⅳ to class Ⅰ-Ⅱ after the procedure in 3 congestive heart failure patients.The right atrium systolic pressure was significantly reduced after the procedure((8.7±1.8) mmHg (1 mmHg=0.133 kPa) vs. (24.3±2.3) mmHg, P=0.03). The diameter of the false aneurysm reduced in 1 patient after the procedure. Complete thrombosis formation of the thoracic false lumen was observed in 1 patient. Conclusion: Transcatheter closure of anastomotic leakage after aortic surgery using AVP Ⅲ is feasible and effective according to our primary experience.


Comparison of morphological changes of muscle fibers in response to dynamic electrical muscle contraction and dynamic hydraulic stimulation in a rat hindlimb disuse model.
This study attempted to compare the muscle fiber morphological responses to dynamic electrical muscle stimulation (DEMS) and dynamic hydraulic stimulation (DHS) in rats under hindlimb suspension (HLS). DEMS at 1 Hz, 50 Hz and 100 Hz for 10 min/day, 5 days/week were introduced to the animals' right quadriceps. Static and 2 Hz DHS were introduced to the right tibiae of other animal groups on a "10 min on - 5 min off - 10 min on" loading regime for 5 days/week. In the end of the 4-week experiments, histological changes in the corresponding soleus, gastrocnemius and quadriceps of the stimulated sites were examined. Compared to age-matched, HLS led to muscle atrophy and strongly reduced muscle wet weights and averaged cross-sectional fiber areas. Among the tested DEMS frequencies, the averaged cross-sectional quadriceps fiber area in the 50 Hz group was 29 % larger than the 100 Hz group. In contrast, difference in the muscle fiber response to the static and 2 Hz DHS was not observed in either soleus or gastrocnemius. Muscle fiber morphological responses to the active DEMS was in a load frequency dependent manner under disuse condition. Relatively passive compressions, either via static or 2Hz DHS, were unable to induce any difference in the muscle fiber responses under functional disuse.


Measurement of integral absorbed dose by chemical dosimeter in panoramic tomography.
As an aqueous chemical dosimeter for measuring ionizing radiation, the chemical 4,4' (5-chloro-2-thenilidene) bis [N,N-dimethylaniline], a derivative of the leuco triarylmethane compounds was used. This chemical dosimeter is an aqueous solution composed of 10(-4) M leuco compounds, 10(-4) M ferrous ammonium sulfate, 10(-4) M sodium chloride and 7 X 10(-3) M of hydrochloric acid. This solution is colourless but it becomes blue-green or bright blue after irradiation. The optical density of this solution at the main absorption peak of 635 millimicron increases linearly with the increasing x-ray dose of from 50R to 2,000 R and no dose-rate dependence is found from 13.5 R/min to 270 R/min of 60Co gamma-ray, 896 gram rads was the measured value of the integral absorbed dose per exposure in panoramic tomography (Orthopantomograph type OP-2).


QSP Toolbox: Computational Implementation of Integrated Workflow Components for Deploying Multi-Scale Mechanistic Models.
Quantitative systems pharmacology (QSP) modeling has become increasingly important in pharmaceutical research and development, and is a powerful tool to gain mechanistic insights into the complex dynamics of biological systems in response to drug treatment. However, even once a suitable mathematical framework to describe the pathophysiology and mechanisms of interest is established, final model calibration and the exploration of variability can be challenging and time consuming. QSP models are often formulated as multi-scale, multi-compartment nonlinear systems of ordinary differential equations. Commonly accepted modeling strategies, workflows, and tools have promise to greatly improve the efficiency of QSP methods and improve productivity. In this paper, we present the QSP Toolbox, a set of functions, structure array conventions, and class definitions that computationally implement critical elements of QSP workflows including data integration, model calibration, and variability exploration. We present the application of the toolbox to an ordinary differential equations-based model for antibody drug conjugates. As opposed to a single stepwise reference model calibration, the toolbox also facilitates simultaneous parameter optimization and variation across multiple in vitro, in vivo, and clinical assays to more comprehensively generate alternate mechanistic hypotheses that are in quantitative agreement with available data. The toolbox also includes scripts for developing and applying virtual populations to mechanistic exploration of biomarkers and efficacy. We anticipate that the QSP Toolbox will be a useful resource that will facilitate implementation, evaluation, and sharing of new methodologies in a common framework that will greatly benefit the community.


Usability and performance expectancy govern spine surgeons' use of a clinical decision support system for shared decision-making on the choice of treatment of common lumbar degenerative disorders.
Quantitative survey study is the study design. The study aims to develop a model for the factors that drive or impede the use of an artificial intelligence clinical decision support system (CDSS) called PROPOSE, which supports shared decision-making on the choice of treatment of ordinary spinal disorders. A total of 62 spine surgeons were asked to complete a questionnaire regarding their behavioral intention to use the CDSS after being introduced to PROPOSE. The model behind the questionnaire was the Unified Theory of Acceptance and Use of Technology. Data were analyzed using partial least squares structural equation modeling. The degree of ease of use associated with the new technology (effort expectancy/usability) and the degree to which an individual believes that using a new technology will help them attain gains in job performance (performance expectancy) were the most important factors. Social influence and trust in the CDSS were other factors in the path model. r2 for the model was 0.63, indicating that almost two-thirds of the variance in the model was explained. The only significant effect in the multigroup analyses of path differences between two subgroups was for PROPOSE use and social influence (p = 0.01). Shared decision-making is essential to meet patient expectations in spine surgery. A trustworthy CDSS with ease of use and satisfactory predictive ability promoted by the leadership will stand the best chance of acceptance and bridging the communication gap between the surgeon and the patient.


Biomaterials for Regenerative Medicine Approaches for the Anterior Segment of the Eye.
The role of biomaterials in tissue engineering and regenerative medicine strategies to treat vision loss associated with damage to tissues in the anterior segment of the eye has been studied for several years. This has mostly involved replacement and support for the cornea and conjunctiva. These are complex tissues with specific functional requirements for different parts of the tissue. Amniotic membrane (AM) is used in clinical practice to transplant autologous or allogenic cells to the corneal surface. Fibrin gels have also progressed to clinical use under specific conditions. Alternatives to AM such as collagen gels, other natural materials, for example keratin and silks, and synthetic polymers have received considerable attention in laboratory and animal studies. This experience is building a body of evidence to demonstrate the potential of tissue engineering and regenerative medicine in corneal and conjunctival reconstruction and can also lead to other applications in the anterior segment of the eye, for example, the trabecular meshwork. There is a real clinical need for new procedures to overcome vision loss but there are also opportunities for developments in ocular applications to lead to biomaterials innovations for use in other clinical areas.


Distal femoral osteotomy for lateral compartment osteoarthritis of the knee.
Twenty-one patients with lateral compartment osteoarthritis and valgus deformity of the knee underwent distal femoral supracondylar osteotomy (medial closing wedge) between 1983 and 1993 with follow-up ranging from 1 to 8 years. Ten knees had plaster cast immobilization, 5 had fixation with 2 staples supplemented with a plaster cast, and 6 knees had rigid internal fixation with an AO blade plate. Thirty-three percent of patients had a satisfactory result using the HSS score, and 57% had a satisfactory result using the Knee Society Clinical Rating. Fifty-seven percent had a significant complication, including severe knee stiffness requiring manipulation under anesthesia (48%), nonunion/delayed union (19%), infection (10%), and fixation failure (5%). Five (19%) knees required total knee replacement within 5 years of surgery. Satisfactory results were obtained only in those patients who had less severe degrees of osteoarthritis confined to the lateral compartment (grades I to III), adequate correction of valgus deformity (the anatomical axis within 2 degrees from zero), and rigid internal fixation to permit postoperative early mobilization. These results indicate that distal femoral osteotomy is a satisfactory procedure in the young, active patient with osteoarthritis of the lateral compartment of the knee, but requires precise surgical technique and rigid internal fixation.


The cytoplasmic substrate permeation pathway of serotonin transporter.
Serotonin transporter (SERT) catalyzes reuptake of the neurotransmitter serotonin (5-HT) and is a target for antidepressant drugs and psychostimulants. It is a member of a large family of neurotransmitter and amino acid transporters. A recent study using site-directed cysteine modification identified a helical region of the transporter with high accessibility to the cytoplasm. Subsequently, the high resolution structure of LeuT, a prokaryotic homologue, showed that the residues corresponding to this helical region are part of the fifth transmembrane domain. The accessibility of these positions is now shown to depend on conformational changes corresponding to interconversion of SERT between two forms that face the extracellular medium and the cytoplasm, respectively. Binding of the extracellular inhibitor cocaine decreased accessibility at these positions, whereas 5-HT, the transported substrate, increased it. The effect of 5-HT required the simultaneous presence of Na+ and Cl-, which are transported into the cell together (symported) with 5-HT. In light of the LeuT structure, these results begin to define the pathway through which 5-HT diffuses between its binding site and the cytoplasm. They also confirm a prediction of the alternating access model for transport, namely, that all symported substrates must bind together before translocation.


Spontaneous EEG theta activity controls frontal visual evoked potential amplitudes.
Frontal visual evoked potentials (VEPs) were studied in order to extend the application of a recently introduced algorithm for selective averaging of evoked potentials. This algorithm is based on the inverse relationship between amplitudes of alpha or theta components of the spontaneous EEG activity and evoked potential (EP) amplitudes. Stimuli were only applied if the root mean square (RMS) value of the ongoing EEG at the lead F4 was below an individual threshold level ('selective stimulation'). For this comparison, the EEG was filtered in one of the frequency ranges 'alpha', 'theta' and 'alpha and theta', respectively. 'Alpha' and 'alpha-and-theta-dependent' selective stimulation conditions resulted in significant amplitude increases (P < 0.05) at the input reference channel F4 and partly at ipsihemispherical temporal and parietal leads and at Cz. The largest increase of 35% at F4 (P < 0.01) was obtained with visual stimulation during low prestimulus theta activity. We conclude that spontaneous theta activity of the frontal cortex may be a factor influencing the amplitudes of frontal VEPs. A sophisticated analysis of frontal EPs, mainly in the framework of cognitive studies, should consider the theta activity prior to stimulation.


The inter-familiar issues of Greek parents facing childhood cancer.
Cancer as a whole, but especially childhood cancer, creates a number of psychological, social, and family problems as well as practical and financial issues, which every parent is called upon to solve. This study focuses on childhood cancer and aims at a thorough analysis of the physical/organic, psychological, and social problems associated with the parents and relatives of a child with cancer. The special element in pediatric neoplasms is not only the vulnerable population target group, but also the set of secondary effects it has on the environment of the sick child. The research was conducted on a sample of 133 families of children with cancer, and the results were displayed after statistical processing and data analysis with R statistical software. The results of the study confirm with statistically significant data the effect of childhood cancer on the physical, mental, and social health and behavior of the parent. Thus, 53.8% of the respondents stated 5 and above on the 7-point Likert scale for fatigue issues, 55.6% for sleep disorders, 78.1% for stress, and 82.7% for fear. The key findings are characterized by high specificity as it is a unique study that reveals particular aspects of the Greek parent's behavior, mind, and body during the period of their child's illness. Conclusion: The effects of childhood illnesses, particularly when they are severe, such as neoplasms, present a looming threat, ushering in a multitude of adverse alterations in the daily lives of the affected child's family. What is Known - What is New: • We know the effects that a childhood illness brings not only to the sick child, but also to the entire family circle. The new element in the present research is that these data reflect the situation in Greece, for which the research data in this area is quite limited. Our research is one of the few studies that demonstrate with statistical data the change in the psychosomatic health of the parent who has a child with cancer.


[Right heart catheter examination: step by step].
Right heart catheterisation is a frequently used procedure in cardiology and intensive care medicine, especially for the differential diagnosis of pulmonary hypertension, shunt diagnostics and accurate calculation of the important haemodynamic parameters. Various catheters are available for the examination; the most common and safest is the use of a Swan-Ganz catheter. The complete examination includes probing of the right atrium, right ventricle, pulmonary artery and pulmonary capillary bed. In this "step-by-step" article, the authors discuss the practical aspects of this method.


Rapid regrowth of intracranial clear cell meningioma after craniotomy and gamma knife radiosurgery--case report.
A 24-year-old woman underwent craniotomy for falx meningioma (5 cm in diameter) on October 24, 1995. The deepest part of the tumor was located in the anterior horn of the lateral ventricle, which was not resected. The histology was clear cell meningioma (CCM), aggressive in nature. The MIB-1 labeling index was high (11%). She underwent gamma knife (GK) radiosurgery for the residual tumor with an irradiation dose of 16 Gy at the tumor periphery on May 24, 1996. The postradiosurgical course was uneventful. The residual intraventricular tumor gradually decreased in size, but the peripheral portion gradually grew into the diencephalic region. The patient remained in good condition for 5 years until September 2001, when she exhibited memory disturbance and lethargy. Magnetic resonance imaging demonstrated a large tumor (4.5 cm in diameter) in the diencephalon, compressing the optic nerves and fornix. The calculated tumor doubling time was 120 days. A second craniotomy was performed on October 9, 2001. The tumor was totally resected through the anterior transcallosal approach. The histology and the MIB-1 labeling index of the tissue from the second operation did not differ markedly from those of the first operation. Neither tumor recurrence nor metastasis has been observed to date. GK radiosurgery contributed to control of the residual intraventricular tumor, but the peripheral portion of the tumor, which received a relatively low radiation dose (16 Gy), grew rapidly. This suggests that a marginal dose of 16 Gy may not be sufficient for control of CCM.


213Bi-Labeled Prostate-Specific Membrane Antigen-Targeting Agents Induce DNA Double-Strand Breaks in Prostate Cancer Xenografts.
Up to now, prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy mainly focused on β-emitting radionuclides. Herein, two new 213Bi-labeled agents for PSMA-targeted α therapy of prostate cancer (PCa) are reported. The biodistribution of 213Bi-labeled small-molecule inhibitor PSMA I&T and nanobody JVZ-008 was evaluated in mice bearing PSMA-positive LNCaP xenografts. DNA damage response was followed using LNCaP cells and LNCaP xenografts. In vitro, 213Bi-PSMA I&T and 213Bi-JVZ-008 therapy of LNCaP cells led to increased number of DNA double-strand breaks (DSBs), detected as 53BP1 and γH2AX nuclear foci. In vivo, tumor uptake of 213Bi-PSMA I&T and 213Bi-JVZ-008 was 5.75% ± 2.70%ID/g (injected dose per gram) and 2.68% ± 0.56%ID/g, respectively, with similar tumor-to-kidney ratios. Furthermore, both agents induced in vivo DSBs in the tumors, which were detected between 1 hour and 24 hours after injection. 213Bi-PSMA I&T induced significantly more DSBs than 213Bi-JVZ-008 (p < 0.01). 213Bi-PSMA I&T and 213Bi-JVZ-008 showed efficient and rapid tumor targeting and produced DSBs in PSMA-expressing LNCaP cells and xenografts. These promising results require further evaluation of 213Bi-labeled agents with regard to their therapeutic efficacy and toxicity for PCa therapy.


Task- and time-dependent weighting factors in a retrospective exposure assessment of chemical laboratory workers.
A chemical exposure assessment was conducted for a cohort mortality study of 6157 chemical laboratory workers employed between 1943 and 1998 at four Department of Energy sites in Oak Ridge, Tennessee, and Aiken, South Carolina. Previous studies of chemical laboratory workers have included members within professional societies where exposure assessment was either limited or not feasible, or chemical processing employees where laboratory and production workers were combined. Because sufficient industrial hygiene records were unavailable for all four sites, weighted duration of employment was used as a surrogate for the magnitude of exposure. Potential exposure indices were calculated for each worker using number of days employed and weighting factors for frequency of contact and year of employment. A total of 591 unique laboratory job titles indicative of a chemical laboratory worker were collapsed into 18 general job title categories. Through discussions with current and retired workers, along with examination of historical organizational charts and job descriptions, the percentage of time with activities involving the direct handling of chemicals in the laboratory was estimated for each job title category. Scaled weighting factors of 1, 0.6, 0.3, and 0.05 were assigned to the job title categories representing 100%, 60%, 30%, and 5% of daily activities handling chemicals, respectively. Based on limited industrial hygiene monitoring data, personal radiation monitoring records, and professional judgment, weighting factors that declined 4% annually were applied to each year to account for improvements in laboratory technique, advancements in instrumentation, improvement in engineering controls, and increased safety awareness through time. The study cohort was separated into three categories of chemical exposures based on department level information: (1) inorganic, (2) mixed inorganic and organic, and (3) unknown. Potential exposure indices ranged from 0.15 to 6824.5 with a median value of 377.5 and a mean equal to 884.2. This exposure assessment method is useful for epidemiologic analyses when quantitative exposure data are absent or insufficient.


NATURAL SELECTION OF ALLOZYME POLYMORPHISMS: A MICROSITE TEST REVEALING ECOLOGICAL GENETIC DIFFERENTIATION IN WILD BARLEY.
Allozymic variation in proteins encoded by 25 loci was analyzed electrophoretically in 1982 and 1983 in 356 individual plants from a dense population of wild barley, Hordeum spontaneum, the progenitor of cultivated barley. The test involved six microniches organized in a mosaic pattern in the open Tabor oak forest at Neve Ya'ar, Israel. The microniches were i) sun-soil, ii) sun-rock, iii) shade-soil, iv) shade-rock, and the contact zones: v) soil periphery of the sun-rock microniche, and vi) soil periphery of the shade-rock microniche. Discriminant analysis indicated significant multilocus allozymic differentiation between the microniches. Our results suggest that allozyme polymorphisms in wild barley are at least partly adaptive and differentiate predominately by microniche ecological selection, rather than by stochastic processes and/or neutrality of allozymic variants.


Evaluation of α-fetoprotein-L3 and Golgi protein 73 detection in diagnosis of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is common throughout the world. Most HCCs are diagnosed at an advanced stage. There is an urgent need to find new methods for screening and surveillance of individuals at risk for HCC. The aim of this study was to evaluate serum α-fetoprotein (AFP)-L3 and serum Golgi protein 73 (GP73) detection in diagnosis of HCC with different AFP concentration. One hundred and eighty one patients were involved, including 102 with HCC and 79 with benign liver disease. The serum AFP-L3 and GP73 was measured by a liquid-phase binding assay and quantitative enzyme-linked immunosorbent assay, respectively. Of the 102 HCC patients, 53 were positive for AFP, 77 were positive for AFP-L3, and 79 were positive for GP73. The maximum area under the curve for AFP-L3% and for GP73 was significantly different from the AUC of 0.5525 for total AFP (p < 0.01). AFP-L3% was not detected for AFP < 20 ng/ml. However, elevated GP73 was detected in 87.50% of the patients. In the HCC patients with total AFP 20-400 ng/ml, elevated AFP-L3 was detected in 26 patients, whereas in 23 patients elevated GP73 could be detected. In the HCC patients with a total AFP > 400 ng/ml, AFP-L3% > 10% was present in 96.23%, and GP73 was detected in 87.50%. The determination of AFP-L3% and GP73 in combination with AFP can increase the sensitivity and specificity in diagnosis of HCC. α-fetoprotein-L3% and GP73, in combination with AFP, are useful biomarkers to confirm the diagnosis of HCC.


Dealing with negative social exchanges in later life: coping responses, goals, and effectiveness.
Negative exchanges have been shown to detract from psychological well-being in later life, but little research has investigated how older adults respond to such exchanges. The authors examined older adults' coping responses, goals, and effectiveness following a specific negative social exchange. The findings revealed that participants' coping responses and the effectiveness of these responses varied as a function of their coping goals. The results underscore the importance of considering older adults' coping responses and goals when evaluating factors that affect the impact of negative social exchanges on well-being in later life.


Relationship between periodontitis and systemic diseases: leptin, a new biomarker?
Leptin is a polypeptide hormone associated with the occurrence of legion of diseases including obesity, cardiovascular diseases, and diabetes. Periodontitis, that is, inflammation of the periodontium has also been linked to a number of systemic manifestations. The aim of the present study was to analyze the role of leptin as a biomarker linking periodontitis with obesity, cardiovascular diseases, and diabetes. The inclusion criteria included, clinical trials available in English language; studies involving human participants; studies relating leptin and periodontal diseases to either obesity, cardiovascular diseases or diabetes. Exclusion criteria enlisted manuscripts in language other than English; if they were case reports, narrative reviews, personal communication, conference presentations, editorial and expert opinion; experiments not involving humans. We performed a literature search encompassing the time period from January 2000 to May 2013. A systematic search of the Cochrane Library and the Medline through PubMed was performed using the selected keywords/phrases "leptin and periodontitis," "leptin and periodontal diseases," "leptin, periodontitis and obesity," "leptin, periodontitis and cardiovascular diseases," and "leptin, periodontitis, and diabetes." A total of 23 studies was obtained using the selected keywords/phrases. On screening, the chosen studies seven fulfilled the inclusion criteria. Four demonstrated association of leptin with periodontitis and obesity. One study associated cardiovascular diseases and periodontitis through leptin whereas two were found linking leptin, periodontitis, and diabetes mellitus. We could find some positive consociation between the serum concentration of leptin, periodontitis, and systemic diseases including obesity and cardiovascular diseases. The results were conflicting when its relation with diabetes mellitus type 2 was examined, as one study favored the association whereas the other one claimed that there was no effect on the levels of leptin.


Thoracoscopic sympathectomy for palmar hyperhidrosis in children: 21 years of experience at a tertiary care center.
The aim of this study was to find out the outcome of "thoracoscopic sympathectomy" (TS) for palmar hyperhidrosis (PH) in children. To our knowledge, this is the largest experience of TS from the United Kingdom. All patients who underwent TS for PH during the past 21 years were studied retrospectively. A total of 85 procedures were done in 44 children. Ratio of female to male was 4:1. Median age at operation was 12.8 years. Types of operations performed were as follows: bilateral T2-T3 sympathectomy in 87% (38/44), bilateral T2-T5 sympathectomy in 9% (4/44), and right-sided thoracoscopic (left-sided done open) in 1% (0.5/44); operation was not possible in 3% (1.5/44) of cases. No chest drains were used. Median postoperative stay was 2 days (range 1 to 5). Median follow-up time was 1.3 years (range 0.2 to 4.7 years). Only problematic patients were followed up for longer. During follow-up, 21% (9/44) developed severe hyperhidrosis of other parts of body. Seven percent (3/44) of patients developed severe axillary hyperhidrosis (AH) and required T4-T5 sympathectomy later on at a median age of 14.4 years (range 11 to 16 years). Another 9% (4/44) patients developed severe plantar hyperhidrosis. Severe hyperhidrosis of the whole body was seen in 5% (2/44) of the patients. Postoperative complications were seen in 47% (21/44) of the patients. They were as follows: postoperative pain (needing > 48 hours hospital stay) in 18% (8/44); transient Horner syndrome in 18% (8/44-right 5, left 3); and recurrence of PH in 11% (5/44) of cases. In the recurrence group, 7% (3/44) were unilateral (right 2, left 1) and 5% (2/44) were bilateral. Redo operations were performed in 11% (5/44) of cases. Median time to redo was 2.6 years (range 8 months to 4.2 years). All three unilateral recurrent patients underwent respective sided redo. In the bilateral recurrence group (2/44), one patient had bilateral redo (remained dry), whereas the other patient underwent only right-sided operation (remained dry), as that sided operation was difficult and so the other side was not tried. FINAL OUTCOMES: The final outcomes were recurrence 3.5% (3/85-right 2, left 1) and technically failed operation 3.5% (3/85-both sides 1, one side 1). Success rate for thoracoscopic sympathetectomy was 93% (79/85) overall. TS for PH is a safe and feasible operation in children. It is successful in the majority; however, the procedure is not trouble free.


Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers.
Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the C(min) values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.


[Combined bipolar radiofrequency and cementoplasty of bone metastases].
Bone metastases are the most common cause of pain in cancer patients. Pain management in cancer patients, often revealing the disease and always present at advanced stages, is an important and difficult task. Pain is not always properly controlled by high doses of specific medication, radiation therapy or chemotherapy. When these therapies do not provide adequate pain relief, percutaneous neurolysis, infiltrations, alcoholizations and cementoplasty may be considered. More recently RF ablation has been proposed. On weight-bearing bones, RF can be combined with acrylic cement injection. The authors present here this very effective new technique which is complementary to classical pain management techniques.


Treatment of 336 cases of chest trauma.
To summarize the clinical features, diagnosis and treatment of chest trauma. A retrospective analysis was conducted among 336 cases of chest trauma admitted to our hospital from January 2009 to May 2011. Out of all cases, 325 were cured, accounting for 96.7%; 11 died, accounting for 3.3%. Among the dead cases, one died of hemorrhagic shock, three of acute respiratory distress syndrome, three of multiple organ failure, and four of severe multiple traumas. (1) For patients with severe chest trauma, early emergency treatment is crucial to save life. (2) Open thoracic surgery is needed for acute cardiac tamponade, intrapulmonary vascular injuries, progressive intrathoracic bleeding, lung laceration, tracheal breakage, and diaphragmatic injury. In addition, operative timing and method should be well chosen. (3) Pulmonary contusion is one of common complications in chest trauma, for which the combination of strong anti-infection therapy and mechanical ventilation is an effective treatment strategy.


From the Representativeness of Sampled Odors to an Olfactive Camera.
Although representativeness is often a prerequisite when sampling odors, the methods used have never been assessed from the analytical and sensory perspective simultaneously. We validate several critical innovations in the methods used to sample odors, starting with a previously developed static-and-trapped headspace (S&T-HS) cell, to minimize sorptive biases and allow for thermodesorption of trapped odors. The addition of a desorption oven allows for restoration and testing of odors sampled by not only S&T-HS but also other techniques (solid-phase microextraction, headspace sorptive extraction, purge-and-trap headspace). The S&T-HS cell exhibits satisfactory representativeness, much higher than the three other techniques. This allows, for the first time, a proposal to use this technology as an olfactive camera to capture and restore an odor. The method was tested on a sample of a complex fresh ashtray odor.


Generalized Langevin equation with shear flow and its fluctuation-dissipation theorems derived from a Caldeira-Leggett Hamiltonian.
We provide a first-principles derivation of the Langevin equation with shear flow and its corresponding fluctuation-dissipation theorems. Shear flow of simple fluids has been widely investigated by numerical simulations. Most studies postulate a Markovian Langevin equation with a simple shear drag term in the manner of Stokes. However, this choice has never been justified from first principles. We start from a particle-bath system described by a classical Caldeira-Leggett Hamiltonian modified by adding a term proportional to the strain-rate tensor according to Hoover's DOLLS method, and we derive a generalized Langevin equation for the sheared system. We then compute, analytically, the noise time-correlation functions in different regimes. Based on the intensity of the shear rate, we can distinguish between close-to-equilibrium and far-from-equilibrium states. According to the results presented here, the standard, simple, and Markovian form of the Langevin equation with shear flow postulated in the literature is valid only in the limit of extremely weak shear rates compared to the effective vibrational temperature of the bath. For even marginally higher shear rates, the (generalized) Langevin equation is strongly non-Markovian, and nontrivial fluctuation-dissipation theorems are derived.


RF properties of circular-ranging OCT signals.
Circular-ranging optical coherence tomography (CR-OCT) systems that use a time-stepped frequency comb source generate interference fringe signals that are more complex than those of a conventional swept-source OCT system. Here, we define a common terminology for describing these signals, and we develop a mathematical framework that relates the radio-frequency (RF) properties of these fringe signals to the parameters of the frequency comb source. With this framework, we highlight non-intuitive mechanisms whereby the design of the frequency comb source can affect imaging performance. We show, for example, that amplitude-pulsed time-stepped frequency comb sources have a sensitivity advantage over constant power time-stepped frequency comb sources. More broadly, this framework and associated terminology provide a foundation on which to design and optimize time-stepped frequency comb sources and systems.


Major nutrients in the Type A lunch. II. Amounts consumed by students.
Plate waste from Type A school lunches was collected during the period that fifth, seventh, and tenth grade students ate lunch. Twelve elementary, three junior high, and seven high schools distributed among three geographic regions of North Carolina were included in the sample. Nutrients served and nutrients in plate waste were determined by laboratory analyses of two five-day composites of meals and of waste from each school. Nutrients consumed were determined by difference. Relative to the Type A goal, protein intake was highest; riboflavin and vitamin A values were consumed in satisfactory (one-third or more of the allowances) amounts. Younger students consumed adequate iron and calcium, and calcium intake approached adequacy among older students. High school students consumed only 69 per cent of their goal for iron and 75 per cent of the goal of energy value; among the three groups, however, this was the highest percentage of the goal for energy value consumed. Ascorbic acid intake was least satisfactory for fifth and seventh grade students. Overall, fifth graders consumed a significantly (P less than .01) lower percentage of the nutrients served than the two older groups. With a few exceptions, students consumed 80 to 90 per cent of the various nutrients which were served: 62 to 66 per cent of the vitamin A value served was consumed; fifth grade students consumed only 77 per cent of the iron served; and the two younger groups consumed only 69 per cent of the ascorbic acid served. Although the most marked regional differences in nutrients consumed occurred with vitamin A and ascorbic acid, overall elementary students in the eastern region consumed a significantly (P less than .01) higher percentage of nutrients served than did those in other two regions.


Dual-view plane illumination microscopy for rapid and spatially isotropic imaging.
We describe the construction and use of a compact dual-view inverted selective plane illumination microscope (diSPIM) for time-lapse volumetric (4D) imaging of living samples at subcellular resolution. Our protocol enables a biologist with some prior microscopy experience to assemble a diSPIM from commercially available parts, to align optics and test system performance, to prepare samples, and to control hardware and data processing with our software. Unlike existing light sheet microscopy protocols, our method does not require the sample to be embedded in agarose; instead, samples are prepared conventionally on glass coverslips. Tissue culture cells and Caenorhabditis elegans embryos are used as examples in this protocol; successful implementation of the protocol results in isotropic resolution and acquisition speeds up to several volumes per s on these samples. Assembling and verifying diSPIM performance takes ∼6 d, sample preparation and data acquisition take up to 5 d and postprocessing takes 3-8 h, depending on the size of the data.


Is parathyroid hormone-related protein a sensitive serum marker in advanced breast cancer?
To compare already used serum markers in advanced breast cancer, namely erythrocyte sedimentation rate (ESR), carcino-embryonic antigen (CEA), and polymorphic epithelial mucins (e.g. CA15-3) with a newer potential marker: parathyroid hormone related protein (PTHrP). A study group of 33 patients of proven advanced breast cancer was compared with 11 patients with benign breast lumps who were undergoing surgery, and eight patients with humoral hypercalcaemia of malignancy of non-breast origin. ESR, CA15-3, CEA, PTHrP, parathormone (PTH), liver and renal function were measured using commercially available kits. Using given reference ranges, results were classified into normal versus abnormal, and univariate statistical comparisons were made using Fisher's exact test. For multivariate analysis, absolute serum levels were used, and multivariate logistic regression models were employed. By univariate analysis, only CA15-3 (P = 0.007), and CEA (P = 0.004), were significant markers of metastatic disease. By multivariate analysis the only independently significant serum marker was CA15-3 (P = 0.043). PTHrP was neither a sensitive (22%) nor specific (90.1%) serum marker when compared to CEA or CA15-3. ESR was the most sensitive single serum marker (93%). An incidental finding of elevations of serum parathormone was found in as many patients as in the study group as there were elevations of PTHrP. PTHrP would not have revealed any patients with metastatic disease that would not have been predicted by any existing tumour markers including CA15-3, CEA and ESR. The finding of elevated PTH in as many patients as PTHrP indicates the possible need for a study inclusive of other polypeptide hormones as markers in advanced breast cancer.


Simultaneous detection of transgenic DNA by surface plasmon resonance imaging with potential application to gene doping detection.
Surface plasmon resonance imaging (SPRi) was used as the transduction principle for the development of optical-based sensing for transgenes detection in human cell lines. The objective was to develop a multianalyte, label-free, and real-time approach for DNA sequences that are identified as markers of transgenosis events. The strategy exploits SPRi sensing to detect the transgenic event by targeting selected marker sequences, which are present on shuttle vector backbone used to carry out the transfection of human embryonic kidney (HEK) cell lines. Here, we identified DNA sequences belonging to the Cytomegalovirus promoter and the Enhanced Green Fluorescent Protein gene. System development is discussed in terms of probe efficiency and influence of secondary structures on biorecognition reaction on sensor; moreover, optimization of PCR samples pretreatment was carried out to allow hybridization on biosensor, together with an approach to increase SPRi signals by in situ mass enhancement. Real-time PCR was also employed as reference technique for marker sequences detection on human HEK cells. We can foresee that the developed system may have potential applications in the field of antidoping research focused on the so-called gene doping.


The integrated use of individual and family psychotherapy.
For almost thirty years after the development of family therapy, the concurrent use of family and individual psychotherapy was seen as incompatible by leading proponents of each modality. Although recently the literature has revealed an increased willingness to utilize family and individual therapies concurrently, the decision for or against any such combination has been left largely to the intuition or bias of the individual clinician. This paper suggests the concurrent use of family and individual psychotherapies when disturbances of family structure and interaction co-exist with, reinforce, and are maintained by largely ego- syntonic internalized psychopathology (that is, the character defences of individual family members). It provides a rationale for integrating the concurrent therapies, and uses clinical examples to illustrate how each can potentiate the other. There is a discussion of indications and contraindications for the integrated use of concurrent family and individual therapy. From their attempts to apply these principles, the authors conclude that the experience for the family, the individual and the therapists is that the selective and integrated use of concurrent family and individual therapies can achieve more than can either therapy alone--the whole is greater than the sum of the parts.


A trafficking pathway for anthocyanins overlaps with the endoplasmic reticulum-to-vacuole protein-sorting route in Arabidopsis and contributes to the formation of vacuolar inclusions.
Plants produce a very large number of specialized compounds that must be transported from their site of synthesis to the sites of storage or disposal. Anthocyanin accumulation has provided a powerful system to elucidate the molecular and cellular mechanisms associated with the intracellular trafficking of phytochemicals. Benefiting from the unique fluorescent properties of anthocyanins, we show here that in Arabidopsis (Arabidopsis thaliana), one route for anthocyanin transport to the vacuole involves vesicle-like structures shared with components of the secretory pathway. By colocalizing the red fluorescence of the anthocyanins with green fluorescent protein markers of the endomembrane system in Arabidopsis seedlings, we show that anthocyanins are also sequestered to the endoplasmic reticulum and to endoplasmic reticulum-derived vesicle-like structures targeted directly to the protein storage vacuole in a Golgi-independent manner. Moreover, our results indicate that vacuolar accumulation of anthocyanins does not depend solely on glutathione S-transferase activity or ATP-dependent transport mechanisms. Indeed, we observed a dramatic increase of anthocyanin-filled subvacuolar structures, without a significant effect on total anthocyanin levels, when we inhibited glutathione S-transferase activity, or the ATP-dependent transporters with vanadate, a general ATPase inhibitor. Taken together, these results provide evidence for an alternative novel mechanism of vesicular transport and vacuolar sequestration of anthocyanins in Arabidopsis.


14-3-3σ Gene Loss Leads to Activation of the Epithelial to Mesenchymal Transition Due to the Stabilization of c-Jun Protein.
Loss of 14-3-3σ has been observed in multiple tumor types; however, the mechanisms by which 14-3-3σ loss leads to tumor progression are not understood. The experiments in this report demonstrate that loss of 14-3-3σ leads to a decrease in the expression of epithelial markers and an increase in the expression of mesenchymal markers, which is indicative of an induction of the epithelial to mesenchymal transition (EMT). The EMT was accompanied by an increase in migration and invasion in the 14-3-3σ(-/-) cells. 14-3-3σ(-/-) cells show increased stabilization of c-Jun, resulting in an increase in the expression of the EMT transcription factor slug. 14-3-3σ induces the ubiquitination and degradation of c-Jun in an FBW7-dependent manner. c-Jun ubiquitination is dependent on the presence of an intact nuclear export pathway as c-Jun is stabilized and localized to the nucleus in the presence of a nuclear export inhibitor. Furthermore, the absence of 14-3-3σ leads to the nuclear accumulation and stabilization of c-Jun, suggesting that 14-3-3σ regulates the subcellular localization of c-Jun. Our results have identified a novel mechanism by which 14-3-3σ maintains the epithelial phenotype by inhibiting EMT and suggest that this property of 14-3-3σ might contribute to its function as a tumor suppressor gene.


Polymerization polarity of actin.
The actin polymer, like the thin filaments of muscle, is known to be polarized as demonstrated by the well known "HMM decoration" technique to give a "herringbone" pattern pointing in one direction. The question "Does polymer formation proceed unidirectionally, or bidirectionally?" was raised and tested experimentally. Short fragments of actin polymers were prepared, fully decorated with HMM and these decorated fragments were used as initiation centers for further actin polymerization without HMM. The resultant polymers showing both decorated and undecorated portions were examined and found to consist of a large majority of "spears" i.e., the added undecorated polymer extended in the direction opposite to that direction pointed by the "herringbone" pattern. However, a few cases of polymers indicating the opposite direction of polymerization were also found. Analysis leads to the conclusion that actin polymerization is unidirectional, although further experimentation is necessary to establish this completely.


[IgA nephropathy: frequent, but rarely diagnosed].
IgA nephropathy (IgAN) is the most common type of glomerulonephritis in the western world. In the majority of cases, it manifests in adolescence or early adulthood as recurrent macrohematuria, frequently triggered by infections, or persistent microhematuria as well as mild proteinuria, hypertension and/or renal insufficiency. In view of the later, it is not surprising that IgAN is often a chance finding. The majority of affected persons probably never come to medical attention, since in autopsies a prevalence of up to 1% of the population has been reported. About 20-30% of patients with a diagnosis of IgAN suffer from chronic, slowly progressive renal failure. Predictors include the degree of proteinuria and arterial hypertension as well as the established renal impairment at the time of diagnosis. Early identification of this risk group is of particular importance, since adequate therapy can stop or at least retard the progression of renal failure. When end stage renal failure has developed and a renal transplant is performed, about 25% of the patients will experience a clinically relevant recurrence of IgAN with progressive graft dysfunction.


LC-HRMS screening of per- and polyfluorinated alkyl substances (PFAS) in impregnated paper samples and contaminated soils.
High per- and polyfluorinated alkyl substance (PFAS) concentrations have been detected in agricultural soils in Southwest Germany. Discharges of PFAS-contaminated paper sludge and compost are suspected to be the cause of the contamination. Perfluorinated carboxylic acids (PFCAs) have been detected also in groundwater, drinking water, and plants in this area. Recently, previously unknown compounds have been identified by high-resolution mass spectrometry (HRMS). Major contaminants were polyfluorinated dialkylated phosphate esters (diPAPs) and N-ethyl perfluorooctane sulfonamide ethanol-based phosphate diester (diSAmPAP). In this study, HRMS screening for PFAS was applied to 14 soil samples from the contaminated area and 14 impregnated paper samples which were from a similar period than the contamination. The paper samples were characterized by diPAPs (from 4:2/6:2 to 12:2/12:2), fluorotelomer mercapto alkyl phosphates (FTMAPs; 6:2/6:2 to 10:2/10:2), and diSAmPAP. In soil samples, diPAPs and their transformation products (TPs) were the major contaminants, but also FTMAPs, diSAmPAP, and their TPs occurred. The distribution patterns of the carbon chain lengths of the precursor PFAS in soil samples were shown to resemble those in paper samples. This supports the hypothesis that paper sludge is a major source of contamination. The presence of major degradation products like PFCAs, FTSAs, or PFOS and their distribution of carbon chain lengths indicate the activity of biotic or abiotic degradation processes and selective leaching processes from the upper soil horizons.


Emergency obstetric hysterectomy.
To assess the frequency of obstetric hysterectomy, its indications and associated maternal and perinatal morbidity and mortality. The retrospective observational analytical study was conducted at the Department of Obstetrics and Gynaecology, Unit-I, Jinnah Postgraduate Medical Centre, Karachi from January 2003 to December 2009. Records of all patients who had underone hysterectomy at the study centre during the study period were explored for age, parity, booking status indication and the type of operation performed. Maternal and foetal morbidity and mortality were also recorded. SPSS 13.0 was used for statistical analysis. Against the total 44,612 deliveries during the period, 121 hysterectomies were performed for obstetric indications. The frequency of the procedure, as such, was 1 in 368 (0.27%) deliveries. The major indications were ruptured uterus in 57 (47.1%), and severe postpartum haemorrhage due to atony of uterus in 35 (28.9%). Other indications included severe haemorrhage due to placental abnormalities in 14 (11.6%); placenta previa in 3 (2.5%); abruptio placenta in 4 (3.3%); and severe infection following vaginal delivery in 3 (2.5%). Infection was the commonest complication seen in 14 (11.6%) patients. There were 11 (9.0%) maternal deaths and 65 (53.7%) perinatal deaths. Emergency obstetric hysterectomy remains a necessary tool for consultant obstetricians. Acting at the optimal time with clear judgment, and professional surgical technique can reduce morbidity and mortality in such cases.


Single chamber microbial fuel cell (SCMFC) with a cathodic microalgal biofilm: A preliminary assessment of the generation of bioelectricity and biodegradation of real dye textile wastewater.
An air exposed single-chamber microbial fuel cell (SCMFC) using microalgal biocathodes was designed. The reactors were tested for the simultaneous biodegradation of real dye textile wastewater (RTW) and the generation of bioelectricity. The results of digital image processing revealed a maximum coverage area on the biocathodes by microalgal cells of 42%. The atmospheric and diffused CO2 could enable good algal growth and its immobilized operation on the cathode electrode. The biocathode-SCMFCs outperformed an open circuit voltage (OCV), which was 18%-43% higher than the control. Furthermore, the maximum volumetric power density achieved was 123.2 ± 27.5 mW m-3. The system was suitable for the treatment of RTW and the removal/decrease of COD, colour and heavy metals. High removal efficiencies were observed in the SCMFCs for Zn (98%) and COD (92-98%), but the removal efficiencies were considerably lower for Cr (54-80%). We observed that this single chamber MFC simplifies a double chamber system. The bioelectrochemical performance was relatively low, but the treatment capacity of the system seems encouraging in contrast to previous studies. A proof-of-concept experiment demonstrated that the microalgal biocathode could operate in air exposed conditions, seems to be a promising alternative to a Pt cathode and is an efficient and cost-effective approach to improve the performance of single chamber MFCs.


Older Infant-Young Child "Formulas".
The category of "formulas" directed at older infants and toddlers 6 to 36 months of age has increased in prominence over the last years but is characterized by lack of standardization in nomenclature and composition as well as questionable marketing practices. There has been uncertainty and misperception regarding some of the roles of these beverages in ensuring adequate childhood nutrition. The aim of this clinical report is to review the context, evidence, and rationale for older infant-young child formulas, followed by recommendations.


Comparison of texture features derived from static and respiratory-gated PET images in non-small cell lung cancer.
PET-based texture features have been used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing static (3D) and respiratory-gated (4D) PET imaging. Twenty-six patients (34 lesions) received 3D and 4D [18F]FDG-PET scans before the chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Texture features, including Maximal correlation coefficient (MCC), Long run low gray (LRLG), Coarseness, Contrast, and Busyness, were computed within the physician-defined tumor volume. The relative difference (δ3D-4D) in each texture between the 3D- and 4D-PET imaging was calculated. Coefficient of variation (CV) was used to determine the variability in the textures between all 4D-PET phases. Correlations between tumor volume, motion amplitude, and δ3D-4D were also assessed. 4D-PET increased LRLG ( = 1%-2%, p < 0.02), Busyness ( = 7%-19%, p < 0.01), and decreased MCC ( = 1%-2%, p < 7.5 × 10(-3)), Coarseness ( = 5%-10%, p < 0.05) and Contrast ( = 4%-6%, p > 0.08) compared to 3D-PET. Nearly negligible variability was found between the 4D phase bins with CV < 5% for MCC, LRLG, and Coarseness. For Contrast and Busyness, moderate variability was found with CV = 9% and 10%, respectively. No strong correlation was found between the tumor volume and δ3D-4D for the texture features. Motion amplitude had moderate impact on δ for MCC and Busyness and no impact for LRLG, Coarseness, and Contrast. Significant differences were found in MCC, LRLG, Coarseness, and Busyness between 3D and 4D PET imaging. The variability between phase bins for MCC, LRLG, and Coarseness was negligible, suggesting that similar quantification can be obtained from all phases. Texture features, blurred out by respiratory motion during 3D-PET acquisition, can be better resolved by 4D-PET imaging. 4D-PET textures may have better prognostic value as they are less susceptible to tumor motion.


Tetrahydroisoquinoline CXCR4 Antagonists Adopt a Hybrid Binding Mode within the Peptide Subpocket of the CXCR4 Receptor.
The rationale for the structural and mechanistic basis of a tetrahydroisoquinoline (THIQ) based series of CXCR4 antagonists is presented. Using the previously reported crystal structures which reveal two distinct binding sites of CXCR4 defined as the small molecule (IT1t or minor) binding pocket and peptide (CVX15 or major) binding pocket, we hypothesized our THIQ small molecule series could bind like either molecule in these respective receptor configurations (IT1t versus CVX15 based poses). To this end, a thorough investigation was performed through a combination of receptor mutation studies, medicinal chemistry, biological testing, conformational analysis, and flexible docking. Our findings showed that the CVX15 peptide-based CXCR4 receptor complexes (red pose) were consistently favored over the small molecule IT1t based CXCR4 receptor configurations (blue pose) to correctly explain the computational and mutational studies as well as key structural components of activity for these small molecules.


The Metabotropic Purinergic P2Y Receptor Family as Novel Drug Target in Epilepsy.
Epilepsy encompasses a heterogeneous group of neurological syndromes which are characterized by recurrent seizures affecting over 60 million people worldwide. Current anti-epileptic drugs (AEDs) are mainly designed to target ion channels and/or GABA or glutamate receptors. Despite recent advances in drug development, however, pharmacoresistance in epilepsy remains as high as 30%, suggesting the need for the development of new AEDs with a non-classical mechanism of action. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype. Consequently, targeting signaling molecules involved in inflammatory processes may represent new avenues to improve treatment in epilepsy. Nucleotides such as adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate (UTP) are released in the brain into the extracellular space during pathological conditions such as increased neuronal firing or cell death. Once released, these nucleotides bind to and activate specific purinergic receptors termed P2 receptors where they mediate the release of gliotransmitters and drive neuronal hyperexcitation and neuroinflammatory processes. This includes the fast acting ionotropic P2X channels and slower-acting G-protein-coupled P2Y receptors. While the expression and function of P2X receptors has been well-established in experimental models of epilepsy, emerging evidence is now also suggesting a prominent role for the P2Y receptor subfamily in seizure generation and the maintenance of epilepsy. In this review we discuss data supporting a role for the P2Y receptor family in epilepsy and the most recent finding demonstrating their involvement during seizure-induced pathology and in epilepsy.


Experiments with a hollow mask and a reverspective: top-down influences in the inversion effect for 3-D stimuli.
Earlier psychophysical and physiological studies, obtained mostly with two-dimensional (2-D) stimuli, provided evidence for the hypothesis that the processing of faces differs from that of scenes. We report on our experiments, employing realistic three-dimensional (3-D) stimuli of a hollow mask and a scene, that offer further evidence for this hypothesis. The stimuli used for both faces and scenes were bistable, namely they could elicit either the veridical or an illusory volumetric percept. Our results indicate that the illusion is weakened when the stimuli are inverted, suggesting the involvement of top down processes. This inversion effect is statistically significant for the facial stimulus, but the trend did not reach statistical significance for the scene stimulus. These results support the hypothesis that configural processing is stronger for the 3-D perception of faces than it is for scenes, and extend the conclusions of earlier studies on 2-D stimuli.


Ultrastructure of the oocyst wall formation in Eimeria? beauchampi Leger and Duboscq, 1917, a coccidian parasite of Glossobalanus minutus (Kow.) (Enteropneusta, Hemichordata).
The ultrastructure of the developing oocyst of Eimeria? beauchampi Leger and Duboscq, 1917 was studied from the ventral digestive epithelium of the hepatic region of Glossobalanus minutus (Enteropneusta). A possible building mechanism of the oocyst wall is deduced and discussed from the present data and the available literature. During oocyst wall formation a total of 5 membranes were observed at or near the surface of the parasite among which some wall-forming materials will be stored. The origin and fate of such wall-forming materials are discussed and compared with data from other coccidians. The apparently full-formed wall is made up of an outer, dense layer, a median layer showing a labyrinthic-tubular lattice substructure, and an inner, homogeneous and osmiophilic layer. A micropyle measuring 0.35 micron in diameter is also described.


Which Child Will Live or Die in France: Examining Physician Responsibility for Critically Ill Children.
There exists some controversy regarding the roles of parents and physicians for life-support decisions for critically ill children. French medical literature asserts that it is inappropriate for parents to bear such responsibilities. Physicians are commonly responsible for these decisions. The aims of this study were to (a) outline how life-support decisions are made for critically ill children in France; (b) examine the cultural context within which these decisional practices have arisen; and (c) analyse the ethical implications of these practices. Data were obtained in 2004 from consultations with relevant experts, relevant French medical guidelines, French print media, empirical research reports and related seminal publications. Specific themes that were identified included: (1) the physician is responsible for medical decision making for children; (2) French physicians caring for critically ill children bear a societal responsibility for preventing severely 'handicapped' survivors; (3) physician authority is rooted in State responsibility for children's welfare; and (4) active euthanasia is sometimes practised to prevent the creation of 'les handicapés'. These findings highlight ethical concerns that can result from assigning some physicians such largely unquestioned societal moral agency.


Post-Translational Regulation of the RSF1 Chromatin Remodeler under DNA Damage.
Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.


Factors affecting functional outcomes after surgery to repair extensive volar forearm lacerations with nerve injuries identified via quantitative and qualitative methods.
We aimed to investigate factors affecting the functional outcomes of patients with extensive volar forearm lacerations combined with nerve injuries who underwent surgery. Between January 2012 and December 2018, a total of 71 patients (58 males, 13 females; mean age: 41±12.1 years; range, 20 to 66 years) with extensive volar forearm lacerations treated in our center were retrospectively analyzed. Demographic data and injury details of the patients were recorded. The functional results were quantitatively evaluated using the Rosén-Lundborg protocol (RLP) and qualitatively evaluated using the Quick Disability of Arm, Shoulder, and Hand (QuickDASH) scale. The mean follow-up time 69.8±36.7 (range, 18 to 148) months. The mean final RLP and QuickDASH scores were 2.17±0.4 and 8.03±10.55, respectively. There were no major complications such as infection, necrosis, re-rupture of a structure, or amputation. Patients with combined median and ulnar nerve injuries had poorer RLP scores than the others. Patients with combined median and ulnar nerve injuries, combined radial and ulnar arterial injuries, and who were of low education status, had lower QuickDASH scores than the others. The main factors affecting long-term functional outcomes are a combined artery or nerve injury and a low education status. Favorable results can be achieved with the cooperation of experienced surgeons and hand rehabilitation specialists for patients with severe hand injuries.


[Localization of the freezing front in tissue by the ultrasound-A picture technic in cryotherapy].
The knowledge of the depth of infiltration of the freezing front in the treated tissue represented an essential demand for an optimal cryotherapy (sprayfreezing and contactfreezing). The hitherto used invasive measuring methods are connected with a tissue traumatisation and therefore only applicable in a limited way. On that account the non-invasive ultrasound-A-picture-technique was applied for defining the freezing front extension. Its qualification was represented in vitro (gelatin), in living biological tissue (muscle of rabbit), and on the human eye (cryotherapy of the primary glaucoma). The use of the sonography in the cryotherapy can be recommended for other special medical branches too.


Chemokines in angiogenesis.
Chemokines are a family of small heparin-binding proteins, mostly known for their role in inflammation and immune surveillance, which have emerged as important regulators of angiogenesis. Chemokines influence angiogenesis either through recruitment of pro-angiogenic immune cells and endothelial progenitors to the neo-vascular niche or via direct regulation of endothelial function downstream of activation of G-protein coupled chemokine receptors. The dual function of chemokines in regulating immune response and angiogenesis confers a central role in modulating the tissue microenvironment. Therefore, chemokines may constitute attractive targets for therapeutic intervention in several pathological disorders. This review will summarize the current understanding of the role of chemokines in angiogenesis, and give an overview of angiostatic and angiogenic chemokines and their crosstalk with other angiogenic factors.


Polychlorinated biphenyls (PCB 153 and PCB 126) action on conversion of 20-hydroxylated cholesterol to progesterone, androstenedione to testosterone, and testosterone to estradiol 17beta.
To look for one of the possible mechanisms of action we investigated the effect of two congeners of polychlorinated biphenyls (PCB153 as one of the most prominent environmental contaminants and PCB 126 as one of the most toxic contaminants similar to dioxin) on the cellular conversion of steroid precursors as an indicator for enzyme activity (20-hydroxylated cholesterol to progesterone for P450 (scc,) androstendione to testosterone for 17-beta-HSD, and testosterone to estradiol for P450 (arom)). The net synthesis and secretion of particular steroids was used as the indicator of enzyme activity. Co-culture of pig granulosa and theca cells isolated from small (SF) and large (LF) follicles, was carried out in medium M199 supplemented with 100 ng/ml of PCB 153 or 100 pg/ml of PCB 126. The inhibitory action of both PCB 126 and PCB 153 on progesterone secretion by cells isolated from SF and LF follicles was reversed in the presence of 20-hydroxylated cholesterol. The addition of PCB 126 into the culture medium caused a decrease in testosterone secretion by cells isolated from both SF and LF and this effect was reversed in the presence of androstendione. The inhibitory action of PCB 153 on testosterone secretion was reversed by the addition of androstendione to the culture medium in SF, while it caused even additional stimulatory action on cells collected from LF. No effect of PCB 126 and statistically significant decrease in estradiol secretion by cells collected from SF under the influence of PCB153 was observed. The inhibitory effect of PCB 153 was reversed when the culture was supplemented with testosterone. The opposite effect of both tested congeners on estradiol secretion in both basal and testosterone supplemented culture was seen in LF. PCB 126 increased it while PCB 153 decreased both, the basal and testosterone-stimulated estradiol secretion. In conclusion, the presented results suggest that the effect of both PCBs on steroid secretion observed in an early stage of the follicular phase of the estrus cycle is due to the inhibition of cholesterol mobilisation and thus insufficient substrate availability for hormone synthesis. On the contrary, in large preovulatory follicles inhibition of testosterone secretion is due to their action on 17-beta-HSD while stimulatory or inhibitory action on estradiol secretion is the result of their action on P450 aromatase activity.